Environmental spreading of clinically relevant carbapenem-resistant gram-negative bacilli: the occurrence of blaKPC-or-NDM strains relates to local hospital activities

Background Aquatic matrices impacted by sewage may shelter carbapenem-resistant (CR) Gram-negative bacilli (GNB) harboring resistance genes of public health concern. In this study, sewage treatment plants (STPs) servicing well-defined catchment areas were surveyed for the presence of CR-GNB bearing carbapenemase genes (blaKPC or blaNDM). Results A total of 325 CR-GNB were recovered from raw (RS) and treated (TS) sewage samples as well as from water body spots upstream (UW) and downstream (DW) from STPs. Klebsiella-Enterobacter (KE) group amounted to 116 isolates (35.7%). CR-KE isolates were recovered from TS, DW (35.7%) and RS samples (44.2%) (p = 0.001); but not from UW samples. KE isolates represented 65.8% of all blaKPC or blaNDM positive strains. The frequency of blaKPC-or-NDM strains was positively associated with the occurrence of district hospitals located near STPs, as well as with the number of hospitalizations and of sewer connections serviced by the STPs. blaKPC-or-NDM strains were recovered from ST samples in 7 out of 14 STPs, including four tertiary-level STPs; and from 6 out of 13 DW spots whose RS samples also had blaKPC-or-NDM strains. Conclusions Clinically relevant GNB bearing blaKPC-or-NDM resist sewage treatments and spread into environmental aquatic matrices mainly from STPs impacted by hospital activities.

A Five-year retrospective hospital-based study on epidemiological data regarding human Leishmaniasis in West Kordofan state - Sudan

Background Leishmaniasis is a parasitic zoonotic disease caused by the Leishmania parasites genus. The estimation of this disease is very important to inform the health care policymakers and the governments to applied proper health and economic policies. Thus, this study aimed, to find out the frequency and distribution of human leishmaniasis in West Kordofan state, based on sex and age during 5 years- Sudan. Methods Five years retrospective study from 2016 through 2020 was carried out using local hospital records of leishmaniasis patients. The age and gender of each patient were recorded. The collected data were analysed using STATA package version 16. Results A total of 162,443 patient records from 2016 to 2020 were retrieved. Of these, 4.39% were found to be positive for leishmaniasis. The disease has been more common in males (65.3%) than in females (, 34.7%). The highest reported prevalence (6.58%) was in patients 15-44 years old, which was, and the lowest prevalence (1.95%) was among patients in ≥65-year-old. Conclusion The current study indicates that leishmaniasis is endemic in the study area even though the numbers of patients in the five consecutive years were varying. Besides, the disease was common in males and adults.

Therapeutic drug monitoring of thiopurines: Effect of reduced 6-thioguanine nucleotide target levels in IBD patients

Aim: The effect of the Dutch nationwide adjustment of reduced 6-TGN target values (from 600-1200 pmol/8x108 RBC to 320-630 pmol/8x108 RBC) on toxicity and clinical outcome of thiopurine treatment in patients with inflammatory bowel disease (IBD) has not yet been established. Therefore the authors determined the incidence of toxicity-induced discontinuations and efficacy at both target concentrations. Methods: This retrospective study was performed in IBD patients treated with azathioprine or mercaptopurine. Two groups were defined: the former target (FT) group with target concentrations of 600-1200 pmol/8x10^8 RBC and the adjusted target (AT) group with target concentrations of 320-630 pmol/8x10^8 RBC. Patients were followed for maximum 52 weeks or until discontinuation of thiopurine therapy. Data were collected from the local hospital electronic health software of Rijnstate Hospital. Results: 151 patients were included, 76 in the FT group and 75 in the AT group. At week 52, 100 out of 150 patients (66%) of the total population discontinued thiopurine therapy. Forty-eight of this discontinuations were due toxicity (48%). The estimated cumulative incidence of toxicity was higher in the FT group compared to the AT group (47% and 35% respectively, p=0.25). No loss of efficacy was seen in the AT group. Conclusion: Reduction of the target range may lead to less toxicity induced discontinuations. In addition, this study did not find any indication that the reduction of the target range diminished efficacy.

Observational study of clinico-radiological follow-up of COVID-19 pneumonia: a district general hospital experience in the UK

Background The British Thoracic Society (BTS) recommends that all patients admitted with COVID-19 pneumonia should have a chest X-ray (CXR) and clinical follow-up at 6 or 12 weeks, depending on the disease severity. Little data is available on long-term CXR follow-up for moderate and severe COVID-19 pneumonia. This study aims to evaluate compliance with clinico-radiological follow-up of patients recovering from COVID-19 pneumonia at a local hospital in the UK, as per the BTS guidance, and to analyse radiological changes at clinical follow-up at 12 weeks, in order to risk-stratify and improve patient outcomes. Methods This is a single-centre retrospective audit of 255 consecutive COVID-19 positive patients admitted to a local hospital in the UK over 5 months between May and October 2020. All CXRs and clinic follow-up at 12 ± 8 weeks were checked on an electronic database. Results Over one in two (131/255) patients had CXR evidence of COVID-19 pneumonia during the initial hospital admission. Half of the patients (60/131) died before CXR or clinic follow-up. Fifty-eight percent (41/71) of the surviving patients had a follow-up CXR, and only two developed respiratory complications- one had residual lung fibrosis, another a pulmonary embolism. Eighty-eight percent (36/41) of the patients had either resolution or improved radiological changes at follow-up. Most patients who had abnormal follow-up CXR were symptomatic (6/8), and many asymptomatic patients at follow-up had a normal CXR (10/12). Conclusions Although there were concerns about interstitial lung disease (ILD) incidence in patients with COVID-19 pneumonia, most of our patients with COVID-19 pneumonia had no pulmonary complications at follow-up with CXR. This emphasises that CXR, a cost-effective investigation, can be used to risk-stratify patients for long term pulmonary complications following their COVID-19 pneumonia. However, we acknowledge the limitations of a low CXR and clinic follow-up rate in our cohort.

An OxPLORE Initiative Evaluating Children’s Surgery Resources Worldwide: A Cross-sectional Implementation of the OReCS Document

Background The Global Initiative for Children's Surgery (GICS) group produced the Optimal Resources for Children’s Surgery (OReCS) document in 2019, listing standards of children’s surgical care by level of healthcare facilities within low resource settings. We have previously created and piloted an audit tool based on the OReCS criteria in a high-income setting. In this study, we aimed to validate its use in identifying gaps in children’s surgery provision worldwide. Methods Our OReCS audit tool was implemented in 10 hospitals providing children’s surgery across eight countries. Collaborators were recruited via the Oxford Paediatrics Linking Our Research with Electives (OxPLORE) international network of medical students and trainees. The audit tool measured a hospital’s current capacity for children’s surgery. Data were analysed firstly to express the percentage of ‘essential’ criteria met for each specialty. Secondly, the ‘OxPLORE method’ was used to allocate each hospital specialty a level based on procedures performed and resources available. A User Evaluation Tool (UET) was developed to obtain feedback on the ease of use of the tool. Results The percentage of essential criteria met within each category varied widely between hospitals. The level given to hospitals for subspecialties based on OReCS criteria often did not reflect their self-defined level. The UET indicated the audit tool was practicable across multiple settings. Conclusions We recommend the use of the OReCS criteria to identify areas for local hospital improvement and inform national children’s surgical plans. We have made informed suggestions to increase usability of the OReCS audit tool.

IMUP and GPRC5A: two newly identified risk score indicators in pancreatic ductal adenocarcinoma

Background Pancreatic cancer has been a threateningly lethal malignant tumor worldwide. Despite the promising survival improvement in other cancer types attributing to the fast development of molecular precise medicine, the current treatment situation of pancreatic cancer is still woefully challenging since its limited response to neither traditional radiotherapy and chemotherapy nor emerging immunotherapy. The study is to explore potential responsible genes during the development of pancreatic cancer, thus identifying promising gene indicators and probable drug targets. Methods Different bioinformatic analysis were used to interpret the genetic events in pancreatic cancer development. Firstly, based on multiple cDNA microarray profiles from Gene Expression Omnibus (GEO) database, the genes with differently mRNA expression in cancer comparing to normal pancreatic tissues were identified, followed by being grouped based on the difference level. Then, GO and KEGG were performed to separately interpret the multiple groups of genes, and further Kaplan–Meier survival and Cox Regression analysis assisted us to scale down the candidate genes and select the potential key genes. Further, the basic physicochemical properties, the association with immune cells infiltration, mutation or other types variations besides expression gap in pancreatic cancer comparing to normal tissues of the selected key genes were analyzed. Moreover, the aberrant changed expression of key genes was validated by immunohistochemistry (IHC) experiment using local hospital tissue microarray samples and the clinical significance was explored based on TCGA clinical data. Results Firstly, a total of 22,491 genes were identified to express differently in cancer comparing to normal pancreatic tissues based on 5 cDNA expression profiles, and the difference of 487/22491 genes was over eightfold, and 55/487 genes were shared in multi profiles. Moreover, after genes interpretation which showed the > eightfold genes were mainly related to extracellular matrix structural constituent regulation, Kaplan–Meier survival and Cox-regression analysis were performed continually, and the result indicated that of the 55 extracellular locating genes, GPRC5A and IMUP were the only two independent prognostic indicators of pancreatic cancer. Further, detailed information of IMUP and GPRC5A were analyzed including their physicochemical properties, their expression and variation ratio and their association with immune cells infiltration in cancer, as well as the probable signaling pathways of genes regulation on pancreatic cancer development. Lastly, local IHC experiment performed on PAAD tissue array which was produced with 62 local hospital patients samples confirmed that GPRC5A and IMUP were abnormally up-regulated in pancreatic cancer, which directly associated with worse patients both overall (OS) and recurrence free survival (RFS). Conclusions Using multiple bioinformatic analysis as well as local hospital samples validation, we revealed that GPRC5A and IMUP expression were abnormally up-regulated in pancreatic cancer which associated statistical significantly with patients survival, and the genes’ biological features and clinical significance were also explored. However, more detailed experiments and clinical trials are obligatory to support their further potential drug-target role in clinical medical treatment.

The Ratio of NT-proBNP to CysC1.53 Predicts Heart Failure in Patients With Chronic Kidney Disease

Background: The N-terminal pro B type natriuretic peptide (NT-proBNP) is important for prognosis of heart failure in patients with chronic kidney disease (CKD). However, the NT-proBNP level is easily affected by renal insufficiency, which limits its clinical use.Methods: This study included 396 patients with CKD. Plasma levels of NT-proBNP and cystatin C (CysC) were measured during hospitalization. The echocardiographic parameters were also detected. Patients were divided into the heart failure group and control group according to the European Society of Cardiology Guideline on Chronic Heart Failure 2021. Multiple modeling analysis of the values of NT-proBNP and CysC, including NT-proBNP/Cyscn and NT-proBNP/nCysC was performed. The receiver operating characteristic (ROC) curve, combined with the cardiac function, was used to determine the formula with the best diagnostic efficiency. Then, the sensitivity and specificity of new predictors for cardiac insufficiency in CKD patients were calculated. Pearson correlation analysis was used to analyze the relationship between new predictors and the NT-proBNP level. The clinical data of CKD patients from another local hospital were used to validate the new predictors and the cut-off values.Results: An elevated NT-proBNP/CysC1.53 ratio was an independent risk factor for cardiac dysfunction in CKD and the best predictor derived from multiple modeling analysis. There was no correlation between the NT-proBNP/CysC1.53 ratio and the NT-proBNP level (r = 0.376, p = 6.909). The area under the ROC curve for the NT-proBNP/CysC1.53 ratio was 0.815 (95% confidence interval: 0.772–0.858), and for a cut-off point of 847.964, this ratio had a sensitivity of 78.24%, and a specificity of 69.44%. When applied to the data of CKD patients from another local hospital, the NT-proBNP to CysC1.53 ratio had a sensitivity of 70.27% and a specificity of 67.74%.Conclusion: The NT-proBNP to CysC1.53 ratio was superior to NT-proBNP alone for predicting cardiac dysfunction in patients with CKD.

The Impact of the "Super Coombs" Test on Patient Management and Outcomes at a Large Tertiary Care Center: A Retrospective Review

Background: The direct antiglobulin test (DAT) identifies the presence of immunoglobulins and complement on the surface of red blood cells and is used to differentiate immune from non-immune hemolysis. Standard DATs done by conventional methods, using anti-IgG or anti-C3 antihuman globulin (AHG) in tube or gel, are performed routinely by laboratories associated with hospital transfusion services. However, if the standard DAT is negative but a strong clinical suspicion for immune-mediated hemolysis remains, serologic testing at an immunohematology reference lab (IRL) can be performed. Subtle differences in reagents and technique in the IRL may identify red cell-bound antibodies missed at the local hospital-based laboratory. In addition, the clinician can request an enhanced DAT, colloquially referred to as a Super Coombs, as a send-out test. This test can detect antibodies that are not detected by standard methods and that have been reported to cause autoimmune hemolysis, namely IgG bound at low levels, low affinity IgG, and IgA. We conducted a retrospective review of enhanced DATs sent by hematologists at the University of Pittsburgh Medical Center and the Allegheny Health Network to an outside IRL to determine the incidence of new autoantibodies detected by the enhanced DAT and assessed the impact of these results on patient management. Methods: We retrospectively identified patients at our center on whom enhanced DATs were sent from January 2019 to January 2021. Demographic, laboratory, and clinical data were collected and analyzed. Results: Twenty one patients were identified as having enhanced DATs sent to one outside IRL during the two year period. The majority of patients had abnormal clinical laboratory markers of hemolysis (81% with an elevated lactate dehydrogenase, 90% with an undetectable haptoglobin) and a history of immune dysregulation (79%). About 2/3 of the patients had a hemoglobin nadir above 6 g/dL. The median number of DATs performed locally prior to requesting the enhanced DAT evaluation was 2 (5 th to 95 th percentile: 1 - 3). Four out of 21 patients (19%) had previously tested positive at the local IRL by conventional serologic methods and 17 (81%) had tested negative. Among the 21 patients, 7 (33%) had at least one positive test on the enhanced DAT battery, including 5 out of the 17 (29%) who had previously tested negative locally. In 5 out of those 7 patients who tested positive by enhanced methods, the positive tests included standard serologic test done by conventional means. The only specialty serologic tests that yielded positive results was testing done at 4 °C, meant to detect low affinity IgG. The mean (±SD) overall turnaround time from sample collection to receipt of the enhanced DAT results was 3.8 (±1.5) days, the bulk of which was transit time from the local hospital to the outside IRL (2.5 (±1.5) days). Empiric high-dose steroid therapy was started in 68% of the patients prior to receipt of the enhanced DAT results. The median time between the first DAT result at the local IRL and the initiation of high dose steroid therapy was 1.5 (5 th to 95 th percentile: 0 - 12.5) days, while the median time from steroid initiation to the time the enhanced DAT was ordered was 5 (5 th to 95 th percentile: 1-256) days. Four patients were diagnosed with DAT-negative autoimmune hemolytic anemia based on response to steroids, whether complete (Hb ≥ 12 g/dL and normalization of LDH and haptoglobin) or partial (Hb improvement by 2 g/dL and no transfusion requirement), despite negative local and enhanced DAT results (table 1). Patients who had self-limited (2 patients) or subacute, non-severe anemia (5 patients) did not undergo a steroid trial and were diagnosed by non-serologic testing, specifically peripheral blood flow cytometry or bone marrow biopsy. Conclusions: The tests that most often yielded positive results on the enhanced DAT were standard serologic tests, suggesting that differences in timing of sample collection or technique may have explained result disparity between the local and outside IRL. Specialty testing done at 4 °C detects low affinity IgG antibodies bound to red cells, but the clinical significance of these antibodies is unclear. The majority of patients in our cohort underwent an empiric trial of high dose steroids prior to receipt of the enhanced DAT results. For these patients, the response to steroids was the deciding factor in AIHA diagnosis rather than the enhanced DAT results. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

MORTALIDADE FEMININA POR AGRESSÃO: UMA ANÁLISE EPIDEMIOLÓGICA NO ESTADO DO MARANHÃO

O presente trabalho tem por objetivo analisar a mortalidade feminina por agressão no estado do Maranhão, bem como a tendência deste perfil após a vigência da Lei do Feminicídio, Lei 13.104/2015, no período de 2012 a 2018. A base de dados secundários foi o Sistema de Informação sobre Mortalidade – SIM, e Departamento de Informática do Sistema Único de Saúde – DATASUS. As variáveis relacionadas ao perfil da vítima foram idade (>10,< 60); cor da pele (branca, preta, amarela, parda, indígena); causa do óbito; local (hospital ou outro estabelecimento de saúde, domicílio, via pública, outros); Também foram considerados dados socioeconômicos, estado civil, escolaridade, ocupação. Quanto à análise descritiva dos dados, o teste qui-quadrado foi utilizado para comparar o total de casos notificados comparando-os antes e após a implementação da Lei nº 13.104/2015. Quanto à análise da associação das variáveis do estudo, foi aplicado o teste exato de Ficher. As informações obtidas irão fomentar plano de ação para combate a violência contra mulher e ao feminicídio. Os resultados demonstram que neste estado (Maranhão), a maior porcentagem de óbitos foi em mulheres com idades entre 20 e 39 anos (60,2% das mortes no período), que as principais vítimas foram mulheres de cor parda (72,3%) e solteiras (65,5%), o que sugestiona relação com situações de violência doméstica e familiar contra a mulher.

Clinical characteristics of Kawasaki disease in adolescents

Objective Studies focusing on Kawasaki disease (KD) in adolescents are lacking in Southwest China. We systematically summarized the clinical characteristics of KD in adolescents to improve pediatricians’ recognition of this condition. Methods The clinical data of patients with adolescent-onset KD in our center were retrospectively analyzed. The patients were divided into Group A (n = 7), whose first hospitalization was at our hospital, and Group B (n = 10), who were transferred from their local hospital or community health center. Results Seventeen patients with adolescent-onset KD were identified (constituent ratio of 0.8%). Seven patients had an intermittent fever for >10 days. The incidence of incomplete KD was 52.9%. These patients had a high incidence of other atypical clinical manifestations. Fifteen patients were initially misdiagnosed with other infectious diseases. Although the incidence of typical KD was higher in Group B, the overall misdiagnosis rate at the initial stages was higher and the average fever duration on arrival and before IVIG administration were much longer in Group B than A. Conclusions KD in adolescents was frequently misdiagnosed, which might be associated with its atypical, diverse clinical features and pediatricians’ poor recognition. Pediatricians must be aware of the possibility of KD in adolescents.